??????????%20%20%20%20%20Campylobacter

1
?????????? Campylobacter

• C. fetus veneralis
• C. fetus fetus
• C. jejuni / coli

2
??????

• ????? ????, ???????, ???? ????, "???".

• ???? ????? (????? ???)
• ?????? ?????????????? (???? ??????? ???' vibrio
  ??? ??? vibriosis
• ???? ?????? ?????? ??? ?????? ????? ?????? ??
  ???? ?TCA ??? ???? ??????.

3
?????

• ?????? ????? ??????? (????? ??????????? ??????
  (???? ??????? ?? ????)
• 5 ????, 10 CO2 ?- ???? ?? ????
• ????? ????? (48 ???? ?????)

• ??. ??????? ???? ??? ????? ?????

4
????????

• ?. ?'???? Heat labile O antigens ?????? ??????
  ??????? ?????????.
• ?? ?????? ?"? ?????? ???????.

5
????????

• ?. ???? S-layer (surface array proteins)SAP
  ???? ??????? ?? ?????? ?????? ??????? ???????
  ???????????? ???? ???? ???????? ????.
• ?????? ????? 3C ??? ?????? (???? ??????????).
• ????? ???????? ??????? ?????.
• the S-layer confers resistance to complement
  mediated killing in non-immune serum by
  preventing the binding of complement factor C3b
  to the C. fetus cell surface.
• S-layer expressing C. fetus strains remain
  susceptible to complement independent killing,
  utilizing opsonic antibodies directed against the
  S-layer.
• ??????? ????? ???-????? ?? ??????? ??? ?????? ??
  ???????????? ??? ?????? ???-?????? ????????? ????
  ?? ?????? ?-O ?? ?-LPS ?? ??????? ???.

6
????? ??????

• Motility and chemotaxis
• Chemoattraction towards bile and mucin allows
  colonization of the intestine and gall bladder
• adherence to epithelial cells
• Adherence with proteins, flagella and
  lipopolysaccharide.
• Campylobacter are adherent to cell membrane and
  are internalized into cytoplasmic vacuoles.
• flagellin and adhesion both are required for
  irreversible binding of bacteria to cells

7
????? ??????

• Intracellular
• C. fetus is capable of adhering, entering, and
  surviving within the nonphagocytic epithelial
  cells
• Proteins and enzymes
• cytolethal distending toxin (CDT) causes cellular
  distention and eventually death of the cell lines
  
• hemolysin.
• Catalase is required for Campylobacter hydrogen
  peroxide resistance as well as persistence in
  macrophages

8
Cell Wall

• typical of gram-negative cells.
• three layers,
• an outer lipoprotein layer,
• a middle lipopolysaccharide layer
• inner mucopeptide layer.
• The LPS consisted of three distinct regions
• lipid A anchored in the outer membrane and is the
  endotoxic part of the LPS molecule.
• the core, which is attached to the lipid
• the O antigen attached to the outer core.
• The LPS molecules of Campylobacter are involved
  in adherence and play a role in antigenic
  variations, as Campylobacter has the ability to
  shift the LPS antigenic composition.
• Surprisingly N-acetyl neuraminic acid (sialic
  acid) is present in the core oligosaccharide, not
  frequently found in prokaryotes. These sialic
  acid residues appeared like gangliosides in
  structure, when attached to D galactosidase.
• This molecular mimicry is involved in the
  neuropathological autoimmune diseases like
  Guillains Barre' Syndrome and Reiter syndrome.

9
????? ????

• C. f. veneralis ???? ???? ????????? ?? ??????
  ????? ???' ???? ????? ?????? (???? ???? ?????,
  ????? ????, ???? ?????????) .
• C.fetus fetus ???? ???? ???? ??? ??' ?????? ?????
  ?????? ?????? ????????, ???? ???? ????? ?????.
• ????? ?????? commensals ?? ??' ?????? ?? ????,
  ???, ?????, ????? ????? ???? ?????.

10
Survival in the Environment

• Survival of C. jejuni outside the gut is poor,
  and replication does not occur readily.
• C. jejuni grows best at 37C to 42C, the
  approximate body temperature of the chicken (41C
  to 42C).
• C. jejuni grows best in a low oxygen or
  microaerophilic environment, such as an
  atmosphere of 5 O2, 10 CO2, and 85 N2.
• The organism is sensitive to freezing, drying,
  acidic conditions (pH lt 5.0), and salinity.

11
????????

• C. jejuni / C.coli
• ????? ???????? (invasive ) ??? ????? ??????? ??
  ???? ??? ?????? ?? ??' ??????. ????? (chemotaxis
  ) ?????? (mucin ) ???? ?????? ?????? ?? ???,
  ?????? ????? ????? ????.
• ????? ?????? ????? ????????? (?????). ????? ???
  ????? ??? ???? ??? ?????? ??????? ????? ???????
  ????? ???? ( ??? ??????, ??? ???? ????).
• produces an adhesin, a cytotoxin and a heat
  labile toxin (LPS) similar to E. coli.

12
????, ???, ????? C. jejuni

• ???? ???' ?????? ??? ?????? ???????.
• ????? ????????.
• ???? ??? ??????.

13
??????

• ??? ??? ??????
• ???? ????? ????, ???? ?? ?? ??? ??.

?????

• ?????? ???? ????? ????? ?????, ????
• ?????? ??? ??? ?????? ???????

14
?????

• ????? ????-??????

• ??????
• ????, ????? ????, ?????? ???, ?????, ??? ???, ???
  ???, ??? ?? ??????, ???, ????? ???????, ?????
  ????.
• ????? ?????? ?"? ??????
• ??? ?? ????? ???"? ?? ??"? ?? ????.

15
???? ??? C. jejuni

• ?????, ???, ???? ??? ??????, ?????
• ??? ?????? ??? 1000/100,000 ???.

• ?? ????? ???' ?????? ????? ????????, ????? ?????,
  ??' ????, ????? ????, ???????????, ???? ????,
  ?????, ????? ?????.
• ??????? ???? ??? ??????? ?? acute polyneuropathy
  ?"? Guillain-Barré.

16
Disease Prevalence

• In the United States, an estimated 2.1 to 2.4
  million cases of human campylobacteriosis
  (illnesses ranging from loose stools to
  dysentery) occur each year.
• Commonly reported symptoms of patients with
  laboratory-confirmed infections (a small subset
  of all cases) include diarrhea, fever, and
  abdominal cramping.
• In one study, approximately half of the patients
  with laboratory-confirmed campylobacteriosis
  reported a history of bloody diarrhea.
• Less frequently, C. jejuni infections produce
  bacteremia, septic arthritis, and other
  extraintestinal symptoms.
• Centers for Disease Control and Prevention/U.S.
  Department of Agriculture/Food and Drug
  Administration Collaborating Sites Foodborne
  Disease Active Surveillance Network, 1996

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  PRESS CONTACTDonita Croft, MD, MSWisconsin Division of Public Health(608) 2679004
Outbreak of Campylobacter jejuni Infections
Associated with Drinking Unpasteurized Milk
Procured Through a Cow-Leasing Program ?
Wisconsin, 2001
During November and December 2001, seventy-five
persons from Northwestern Wisconsin became ill
with Campylobacter jejuni enteritis. This
outbreak was associated with drinking
unpasteurized milk obtained through a cow-leasing
program that was used to circumvent regulations
prohibiting the sale of unpasteurized milk in
Wisconsin. Consumers paid an initial fee to lease
part of a cow. Farm operators then milked the
cows and stored the milk from all leased cows
together in a bulk tank. Customers either picked
up milk at the farm or farm operators had it
delivered. To ensure that unpasteurized milk will
not be distributed to the public in Wisconsin,
state officials are enforcing existing
regulations and prohibiting cow-leasing systems.
For more information on Campylobacter visit this
CDC website.
18
Telegraph UK More than 160 mountain bikers made
sick by sheep droppings 02 Dec 2008

•  
• Public health inspectors were called in after the
  cyclists fell ill with food poisoning after an
  event in the Welsh countryside . The cyclists
  tested positive for the bacterium campylobacter
  usually caused by uncooked meat and poultry. But
  following an investigation by health experts, the
  muddy mountain cycle course was found to be
  heavily contaminated with sheep droppings. The
  cyclists are believed to have been affected by
  eating meals and snacks during the event
  without washing their hands first.
• "At that point we launched an internet based
  questionnaire to investigate the outbreak." More
  than 660 mountain bikers from all over Britain
  took part in the Builth Wells Mountain Biking
  Marathon in Powys in July this year. A total of
  355 responses were received with 161 cyclists
  reporting symptoms such as diarrhoea and
  vomiting.
• The report, by the NPHSW, concluded the outbreak
  was caused by campylobacter spread to the
  cyclists by mud which was contaminated with sheep
  faeces. Heavy overnight rain is likely to have
  contributed to the outbreak by increasing the
  amount of liquid mud on the course. The report
  recommended cyclists to eat out of protective
  wrappers at future events.

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Sequelae to Infection

• Guillain-Barré syndrome (GBS), a demyelating
  disorder resulting in acute neuromuscular
  paralysis, is a serious sequela of Campylobacter
  infection. An estimated one case of GBS occurs
  for every 1,000 cases of campylobacteriosis.
• Up to 40 of patients with the syndrome have
  evidence of recent Campylobacter infection .
• Approximately 20 of patients with GBS are left
  with some disability, and approximately 5 die
  despite advances in respiratory care.

Allos BM. Association between Campylobacter
infection and Guillain-Barré syndrome. J Infect
Dis 1997176S125-8.
20
GBS Pathogenesis

• precise mechanism of GBS is unclear.
• certainly has an immunological basis
• most likely an autoimmunity triggered by an
  exogenous antigen.
• It has been linked epidemiologically to
  Campylobacter jejuni as well as other infectious
  agents.
• The preceding infection creates an immunological
  response to proteins epitopically similar to
  myelin.

21
Sequelae to Infection Reiter syndrome

• Campylobacteriosis is also associated with Reiter
  syndrome, a reactive arthropathy. In
  approximately 1 of patients with
  campylobacteriosis, the sterile postinfection
  process occurs 7 to 10 days after onset of
  diarrhea.
• Multiple joints can be affected, particularly the
  knee joint. Pain and incapacitation can last for
  months or become chronic.
• Both GBS and Reiter syndrome are thought to be
  autoimmune responses stimulated by infection.
• The pathogenesis of GBS and Reiter syndrome is
  not completely understood.

Peterson MC. Rheumatic manifestations of
Campylobacter jejuni and C. fetus infections in
adults. Scand J Rheumatol 199423167-70.
22
A survey of Campylobacter in animals.Manser PA,
Dalziel RW.,Hyg (Lond). 1985 Aug95(1)15-21

• A survey of Campylobacter species in the faeces
  or rectal contents of domestic animals was
  carried out using direct and enrichment culture
  methods.
• Campylobacters were isolated from 259 (31) of
  846 faecal specimens.
• The highest isolation rate was found in pigs
  (66) cattle (24) and sheep (22). In pigs all
  the isolates were C. coli, in sheep and cattle
  about 75 were C. jejuni.
• Only five isolations of C. fetus subsp. fetus
  were made, all from cattle. More pigs with
  diarrhoea had C. coli in their faeces than
  healthy pigs (77 vs 47), but such a clear
  difference in isolation rate between sick and
  healthy animals was not seen in cattle or sheep.
• The results show that cattle, sheep and pigs
  constitute a large potential source of
  campylobacter infection for man.

23
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• ?????? ????? ???? ?????? ?????? ???? ?1.6 ?? 28
  ?????? ??? ?????? ???????.
• ??????? ?? ?????? ??????? ???? ??????
• ????? ???? ?? ???, ??? ????? ??
• ?????
• ???? ??????
• /- ???
• ???? ??"? 3-7 ???? ?? ???? ????? ???????? ????
  ??????

24
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25
Antimicrobial Resistance

• The increasing rate of human infections caused by
  antimicrobial-resistant strains of C. jejuni
  makes clinical management of cases of
  campylobacter more difficult.
• Antimicrobial resistance can prolong illness and
  compromise treatment of patients with bacteremia.
• The rate of antimicrobial-resistant enteric
  infections is highest in the developing world,
  where the use of antimicrobial drugs in humans
  and animals is relatively unrestricted.

• Piddock LJV. Quinolone resistance and
  Campylobacter spp. Antimicrob Agents Chemother
  199536891-8.
• Jacobs-Reitsma WF, Kan CA, Bolder NM. The
  induction of quinolone resistance in
  Campylobacter bacteria in broilers by quinolone
  treatment. In Campylobacters, helicobacters, and
  related organisms. Newell DG, Ketley JM, Feldman
  RA, editors. New York Plenum Press 1996. p.
  307-11.

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Antimicrobial Resistance

• Experimental evidence demonstrates that
  fluoroquinolone-susceptible C. jejuni readily
  become drug-resistant in chickens when these
  drugs are administered.
• After flouroquinolone use in poultry was approved
  in Europe, resistant C. jejuni strains emerged
  rapidly in humans during the early 1990s.
• Similarly, within 2 years of the 1995 approval of
  fluoroquinolone use for poultry in the United
  States, the number of domestically acquired human
  cases of ciprofloxacin-resistant
  campylobacteriosis doubled in Minnesota.

Smith KE, Besser JM, Leano F, Bender J, Wicklund
J, Johnson B, et al. Fluoroquinolone-resistant
Campylobacter isolated from humans and poultry in
Minnesota abstract. Program of the 1st
International Conference on Emerging Infectious
Diseases Atlanta, Georgia 1998 Mar 7-10.
Atlanta Centers for Disease Control and
Prevention1998.
27
Campylobacter fetus subsp veneralis

• ??? ????

???
??
Campylobacter fetus subsp fetus
?????, ?????, ??????
???
???
???? ??????
????? ??????
???? ??????
??? ?????
??? ??????
???
???
28
C. fetus veneralis

• ????? ???' ???? ??? ????? ???? ??? ???? ????? ??
  ??????????? ??????? ??????????. ???? ???????
  ???????????, ???? ?????? ???? ?????? ???? ????
  ????????
• cranial vagina, cervix, uterus and oviducts ?
• subacute endometritis with periglandular
  lymphocytic infiltration

29
C. fetus veneralis

• ????? ?? IgG ???? ?- IgA ????? ??????? ?????
  ????? ?????. ( ??? ?? ???)
• ??? ????? ??? ?? ??' ?????? ????????.
• ????? ????? ?????? ?????? ?????? ????????????
  ????? ???.

30
?????? ??????

• ???? ?? - ?????? ???? ?? ?????
• ???? ???????
• ???? ?????? - ????? ?????
• ??? ????? (??"? ???? ?10 )
• ????? ??? ????? ???? ????.

31
C. f. fetus

• ????? ???- ?????
• ??"? ???? ?????? ?????? ????
• ????? ? ??????? ???? ????
• ????? ? ???????? ?? ??? ? ???? ????? ???? ?
  ?????? ? ?????

32
Campylobacter fetus in man

• Campylobacter fetus subsp veneralis
• Few cases documented in man
• Debilitating factors (pregnancy, alcoholism,
  neoplasia, cardiac dis.
• Campylobacter fetus subsp fetus
• Septicemia
• 17 - 43 die
• Abortion, premature birth, full term birth which
  up to 50 may die of meningoencephalitis

33
?????? ??????

• ????? ?????? ?????.
• ????? ??? ?????? ?"? ?????? ?????????, ??????
  ?????? ???????? ?? ???????, ?????? ? 25 ?? 42
  ?????.
• ??? ???.
• ?????????????????
• ???? ??????? - ?????- ?? ????
• PCR

34
????? ??????

• ?. ?????? ????? ???????? ????? ?????.
• ??????????? ???? ???? ????? ?? ??????.
• ????? ???'? ??????????????
• ?????- ???? ???'????

35
?. ???? ????

• ???? ?????
• ????? ??????????????, ???????
• ????? ????? ????
• ??? ????? ????? ?????? ????????

36
?. ?'????

• ??"? ??? ???? ??????.
• ????? ??????? ?????? ??????????? ??????? ?????
  ???? ?????? ???? ???.
• ???? ??? ???? ????? ????? ?????? ??? ????.

37
Control of Campylobacter Infection

• On the Farm
• Control of Campylobacter contamination on the
  farm may reduce contamination of carcasses,
  poultry, and red meat products at the retail
  level.
• Epidemiologic studies indicate that strict
  hygiene reduces intestinal carriage in
  food-producing animals.
• In field studies, poultry flocks that drank
  chlorinated water had lower intestinal
  colonization rates than poultry that drank
  unchlorinated water.
• Experimentally, treatment of chicks with
  commensal bacteria and immunization of older
  birds reduced C. jejuni colonization.
• Because intestinal colonization with
  campylobacters readily occurs in poultry flocks,
  even strict measures may not eliminate intestinal
  carriage by food-producing animals.

Stern NJ. Mucosal competitive exclusion to
diminish colonization of chickens by
Campylobacter jejuni. Poult Sci 199473402-7.
Widders PR, Perry R, Muir WI, Husband AJ, Long
KA. Immunization of chickens to reduce intestinal
colonization with Campylobacter jejuni. Br Poult
Sci 199637765-8.
38
Important Tip!

• Protect yourself against getting Campylobacter
  from animals.
• Simply wash your hands with running water and
  soap after any contact with animals and animal
  feces (stool).